B lymphocyte chemotaxis regulated in association with microanatomic localization, differentiation state, and B cell receptor engagement.
Migration of mature B lymphocytes within secondary lymphoid organs and recirculation between these sites are thought to allow B cells to obtain T cell help, to undergo somatic hypermutation, to differentiate into effector cells, and to home to sites of antibody production. The mechanisms that direct migration of B lymphocytes are unknown, but there is evidence that G protein-coupled receptors, and possibly chemokine receptors, may be involved. Stromal cell- derived factor (SDF)-1alpha is a CXC chemokine previously characterized as an efficacious chemoattractant for T lymphocytes and monocytes in peripheral blood. Here we show with purified tonsillar B cells that SDF-1alpha also attracts naive and memory, but not germinal center (GC) B lymphocytes. Furthermore, GC B cells could be converted to respond to SDF-1alpha by in vitro differentiation into memory B lymphocytes. Conversely, the migratory response in naive and memory B cells was significantly reduced after B cell receptor engagement and CD40 signaling. The receptor for SDF-1, CXC chemokine receptor 4 (CXCR4), was found to be expressed on responsive as well as unresponsive B cell subsets, but was more rapidly downregulated on responsive cells by ligand. Finally, messenger RNA for SDF-1 was detected by in situ hybridization in a layer of cells surrounding the GC. These findings show that responsiveness to the chemoattractant SDF-1alpha is regulated during B lymphocyte activation, and correlates with positioning of B lymphocytes within a secondary lymphoid organ.
Bleul
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The Center for Blood Research and Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA.
Schultze
J L
JL
Springer
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TA
D000199:Actins / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D018925:Chemokines / Q000502:physiology*; D019743:Chemokines, CXC; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000378:metabolism
D000199:Actins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D019718:Receptors, CXCR4